This drug interaction study in HIV-infected patients sought to characterize the pharmacokinetics of stavudine (D4T) when given alone and in combination with three drugs commonly used to manage opportunistic infections. Ten patients (1 female, 9 males) were enrolled in the study: 8 Caucasians, 1 Hispanic, and 1 African-American. The mean CD4 count at enrollment was 62 cells/mm3 (range 9-143). There were 2 Grade III toxicities: 2 patients had neutropenia, presumably due to their (trimethoprim/sulfamethoxazole) prophylaxis. These episodes were resolved by switching the patients to aerosolized pentamidine. Adverse effects by study medication included (1) for D4T, 1 patient reported peripheral neuropathy; (2) for clarithromycin, 4 patients reported "bad taste," 3 reported gastrointestinal symptoms, and I reported rash; (3) for rifabutin, 1 patient reported rash; and (4) for fluconazole and ganciclovir, 3 patients each reported gastrointestinal symptoms. As of January 1997, only the D4T levels have been analyzed. Combinations of fluconazole, rifabutine, clarithromycin, and ganciclovir did not significantly alter the peak D4T level, D4T area under the curve, or time to maximum D4T level. These findings suggest that these drugs can be safely used in combination with D4T. Pharmacokinetic studies of the concomitant drug levels are ongoing; final results are expected in the next 3-4 months.